tbuckley/cabot-search huggingface dataset:
Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial
Authors: William E. Russell, Brian N. Bundy, Mark S. Anderson, Laura A. Cooney, Stephen E. Gitelman, Robin S. Goland, Peter A. Gottlieb, Carla J. Greenbaum, Michael J. Haller, Jeffrey P. Krischer, Ingrid M. Libman, Peter S. Linsley, S. Alice Long, Sandra M. Lord, Daniel J. Moore, Wayne V. Moore, Antoinette M. Moran, Andrew B. Muir, Philip Raskin, Jay S. Skyler, John M. Wentworth, Diane K. Wherrett, Darrell M. Wilson, Anette-Gabriele Ziegler, Kevan C. Herold
Journal: Diabetes Care (2023)

OBJECTIVE Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P &amp;lt; 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P &amp;lt; 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.
Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes
Authors: R. Paul Wadwa, Zachariah W. Reed, Bruce A. Buckingham, Mark D. DeBoer, Laya Ekhlaspour, Gregory P. Forlenza, Melissa Schoelwer, John Lum, Craig Kollman, Roy W. Beck, Marc D. Breton
Journal: New England Journal of Medicine (2023)

Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear.In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes.A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group.In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).
Conventional vs Minimally Invasive Breast Surgery—Reply
Authors: Andi Wan, Xiaowei Qi, Yi Zhang
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Modulating tumor-stromal crosstalk via a redox-responsive nanomedicine for combination tumor therapy
Authors: Yuxin Zhang, Jie Zhou, Xiaoting Chen, Zhiqian Li, Lei Gu, Dayi Pan, Xiuli Zheng, Qianfeng Zhang, Rongjun Chen, Hu Zhang, Qiyong Gong, Zhongwei Gu, Kui Luo
Journal: Journal of Controlled Release (2023)
Recommendation for Cannabis Use Disorder Diagnosis in a Context of Cannabis for Therapeutic Purposes
Authors: Tammy Chung, Marc L. Steinberg, Mary Barna Bridgeman
Journal: JAMA Psychiatry (2023)

This Viewpoint proposes a model of cannabis use disorder diagnosis in the context of cannabis for therapeutic purposes that is based on DSM-5 model of diagnosing substance use disorder in the context of prescribed medication use.
Cancer‐associated fibroblast‐derived secreted phosphoprotein 1 contributes to resistance of hepatocellular carcinoma to sorafenib and lenvatinib
Authors: Jung Woo Eun, Jung Hwan Yoon, Hye Ri Ahn, Seokhwi Kim, Young Bae Kim, Su Bin Lim, Won Park, Tae Wook Kang, Geum Ok Baek, Moon Gyeong Yoon, Ju A Son, Ji Hyang Weon, Soon Sun Kim, Hyo Jung Cho, Jae Youn Cheong
Journal: Cancer Communications (2023)

Abstract Background Cancer‐associated fibroblasts (CAFs) play an important role in the induction of chemo‐resistance. This study aimed to clarify the mechanism underlying CAF‐mediated resistance to two tyrosine kinase inhibitors (TKIs), sorafenib and lenvatinib, and to identify a novel therapeutic target for overcoming TKI resistance in hepatocellular carcinoma (HCC). Methods We performed a systematic integrative analysis of publicly available gene expression datasets and whole‐transcriptome sequencing data from 9 pairs of CAFs and para‐cancer fibroblasts isolated from human HCC and para‐tumor tissues, respectively, to identify key molecules that might induce resistance to TKIs. We then performed in vitro and in vivo experiments to validate selected targets and related mechanisms. The associations of plasma secreted phosphoprotein 1 (SPP1) expression levels before sorafenib/lenvatinib treatment with progression‐free survival (PFS) and overall survival (OS) of 54 patients with advanced HCC were evaluated using Kaplan‐Meier and Cox regression analysis. Results Bioinformatic analysis identified CAF‐derived SPP1 as a candidate molecule driving TKI resistance. SPP1 inhibitors reversed CAF‐induced TKI resistance in vitro and in vivo. CAF‐derived SPP1 activated rapidly accelerated fibrosarcoma (RAF)/mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) through the integrin‐protein kinase C‐alpha (PKCα) signaling pathway and promoted epithelial‐to‐mesenchymal transition (EMT). A high plasma SPP1 level before TKI treatment was identified as an independent predictor of poor PFS ( P = 0.026) and OS ( P = 0.047) in patients with advanced HCC after TKI treatment. Conclusions CAF‐derived SPP1 enhances TKI resistance in HCC via bypass activation of oncogenic signals and EMT promotion. Its inhibition represents a promising therapeutic strategy against TKI resistance in HCC. Moreover, plasma SPP1 level before TKI treatment represents a potential biomarker for treatment response prediction.
Natural History and Intervention Thresholds for Ascending Thoracic Aortic Aneurysm—Not an Easy Nut to Crack—Reply
Authors: Matthew D. Solomon, David H. Liang, Alan S. Go
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Application of smart devices in investigating the effects of air pollution on atrial fibrillation onset
Authors: Cong Liu, Meihui Tai, Jialu Hu, Xinlei Zhu, Weidong Wang, Yutao Guo, Haidong Kan, Renjie Chen
Journal: npj Digital Medicine (2023)

Few studies have examined the link between short-term exposure to air pollutants and atrial fibrillation (AF) episodes. This study aims to examine the association of hourly criteria air pollutants with AF episodes. We employ a smart device-based photoplethysmography technology to screen AF from 2018 to 2021. Hourly concentrations of six criteria air pollutants are matched to the onset hour of AF for each participant. We adopt a time-stratified case-crossover design to capture the acute effects of air pollutants on AF episodes, using conditional logistic regression models. Subgroup analyses are conducted by age, gender, and season. A total of 11,906 episodes of AF are identified in 2976 participants from 288 Chinese cities. Generally, the strongest associations of air pollutants are present at lag 18-24 h, with positive and linear exposure-response relationships. For an interquartile range increase in inhalable particles, fine particles, nitrogen dioxide, and carbon monoxide, the odds ratio (OR) of AF is 1.19 [95% confidential interval (CI): 1.03, 1.37], 1.38 (95%CI: 1.14, 1.67), 1.60 (95%CI: 1.16, 2.20) and 1.48 (95%CI: 1.19, 1.84), respectively. The estimates are robust to the adjustment of co-pollutants, and they are larger in females, older people, and in cold seasons. There are insignificant associations for sulfur dioxide and ozone. This nationwide case-crossover study demonstrates robust evidence of significant associations between hourly exposure to air pollutants and the onset of AF episodes, which underscores the importance of ongoing efforts to further improve air quality as an effective target for AF prevention.
Assessment of Clinical Response to Anifrolumab in Patients With Refractory Discoid Lupus Erythematosus
Authors: Katharina Shaw, Stephanie Sanchez-Melendez, Dustin Taylor, Julia Barker, Avery LaChance, Neda Shahriari, Ruth Ann Vleugels
Journal: JAMA Dermatology (2023)

This case series examines the efficacy of anifrolumab as a therapeutic option for patients with lupus erythematosus.
Security and Sharing of NIPT Data Are the Basis of Ethical Decision-Making Related to Non-Medical Traits
Authors: Wenke Yang, Zhenglong Guo, Weili Shi, Litao Qin, Xiaoliang Xia, Bingtao Hao, Shixiu Liao
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was funded by the Province-Ministry Co-construction Major Project on Tackling Key Problems of Henan Provincial Medical Science and Technology Plan (SBGJ202101003); the Doctoral Startup Grant of Henan Provincial People's Hospital (ZC20190149); the Postdoctoral Startup Grant of Henan Provincial People's Hospital (ZC20220268).
Noninvasive Testing for “Non-Medical” Traits: A Misplaced Expressive Concern, Tough Policy Choices
Authors: David Wasserman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making DISCLAIMERThe views expressed in this commentary are the author's alone. They do not represent the positions of policies of NIH or any part of the Federal Government.DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma
Authors: Irene L.M. Reijers, Disha Rao, Judith M. Versluis, Alexander M. Menzies, Petros Dimitriadis, Michel W. Wouters, Andrew J. Spillane, Willem M.C. Klop, Annegien Broeks, Linda J.W. Bosch, Marta Lopez-Yurda, Winan J. van Houdt, Robert V. Rawson, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Sten Cornelissen, Jasper Bouwman, Joyce Sanders, Elsemieke Plasmeijer, Yannick S. Elshot, Richard A. Scolyer, Bart A. van de Wiel, Daniel S. Peeper, Alexander C.J. van Akkooi, Georgina V. Long, Christian U. Blank
Journal: The Journal of Experimental Medicine (2023)

Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies.
Development and Clinical Evaluation of an Artificial Intelligence Support Tool for Improving Telemedicine Photo Quality
Authors: Kailas Vodrahalli, Justin Ko, Albert S. Chiou, Roberto Novoa, Abubakar Abid, Michelle Phung, Kiana Yekrang, Paige Petrone, James Zou, Roxana Daneshjou
Journal: JAMA Dermatology (2023)

Telemedicine use accelerated during the COVID-19 pandemic, and skin conditions were a common use case. However, many images submitted may be of insufficient quality for making a clinical determination.
Role of Vulnerability and Control in Prenatal Testing Ethical Decision-Making
Authors: Renzo Pegoraro, Carlo Casalone, Monica Consolandi
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Association of Surgery With Frailty Status in Older Women With Early-Stage Breast Cancer
Authors: Christina A. Minami, Ginger Jin, Rachel A. Freedman, Mara A. Schonberg, Tari A. King, Elizabeth A. Mittendorf
Journal: JAMA Surgery (2023)

This cohort study examines associations between type of breast cancer surgery and changes in frailty status among US women aged 70 years or older with early-stage breast cancer.
The Slippery Slope of Prenatal Testing for Social Traits
Authors: Courtney Canter, Kathleen Foley, Shawneequa L. Callier, Karen M. Meagher, Margaret Waltz, Aurora Washington, R. Jean Cadigan, Anya E. R. Prince
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was funded by National Human Genome Research Institute under award number 1R01HG012402-01.
Peripheral Auditory Function in Tanzanian Children Living With HIV With Clinically Normal Hearing
Authors: Christopher E. Niemczak, Christin Ealer, Abigail Fellows, Albert Magohe, Jiang Gui, Catherine Rieke, Trent Nicol, Enica R. Massawe, Nina Kraus, Jay C. Buckey
Journal: JAMA Network Open (2023)

Importance Despite normal audiometry, adults living with HIV have lower distortion product otoacoustic emissions (DPOAEs) compared with HIV-negative controls, but the degree of these differences in children living with HIV is unknown. If subclinical auditory deficits are present, results could affect developmental outcomes in children living with HIV (CLWH). Objective To compare DPOAEs and auditory brainstem responses (ABR) between 2 age- and sex-matched groups of younger children with normal audiometry, 1 infected with HIV and the other uninfected. Design, Setting, and Participants Cohort study in an infectious disease center in Dar es Salaam, Tanzania. Participants included 340 Tanzanian children aged 3 to 9 years with clinically normal hearing, type A tympanograms bilaterally, and air-conduction thresholds of 20 dB HL or less from 0.5 to 8 kHz. Participants in the cohort repeated testing approximately every 6 months (approximately 2.2 sessions per participant) for a total of 744 total observations. Data were analyzed from March 2020 to January 2022. Main Outcomes and Measures DPOAE amplitudes from 1.5 to 8 kHz using an f2 to f1 ratio of 1.2 and L1/L2 values of 65/55 dB sound pressure level and click-evoked ABR using a slow (21.1/s) and fast (61.1/s) click rate. Results A total of 141 CLWH (70 female participants [49.3%]; mean [SD] age, 7.24 [1.67] years) and 199 HIV-negative individuals (99 female participants [49.7%]; mean [SD] age, 7.26 [1.44] years) participated in the study. The groups did not differ significantly in age, static immittance, or air-conduction thresholds. HIV status was independently associated with approximately 1.4 dB (95% CI, −3.28 to 0.30 dB) to 3.8 dB (95% CI, 6.03 to −1.99 dB) lower DPOAE amplitudes at 6 and 8 kHz bilaterally and 0.28 μV (95% CI, 0.01 to 0.33 μV) lower ABR wave V amplitudes in the right ear. Conclusions and Relevance Consistent with previous findings in young adults, CLWH had slightly, but reliably, lower DPOAEs and ABR wave V amplitudes than HIV-negative controls. The magnitude of these differences was small, but results suggest an early and consistent association between HIV infection or treatment and outer hair cell and auditory brainstem responses in children as young as 3 years. These subclinical changes suggest tracking both auditory function and development outcomes in CLWH is warranted.
Consistency of What? Appropriately Contextualizing Ethical Analysis of Non-Invasive Prenatal Testing
Authors: Ainsley J. Newson, Zuzana Deans, Lisa Dive, Isabella Catherine Holmes
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image sizeThis article refers to:Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making Additional informationFundingThis work was supported by the Australian Research Council, Discovery Project grant award DP200100006.
The Emerging Value of Circular Noncoding RNA Research in Cancer Diagnosis and Treatment
Authors: Urmila Jagtap, Erik S. Anderson, Frank J. Slack
Journal: Cancer Research (2023)

Abstract Circular RNAs (circRNA) are a recently described class of RNA molecules that have attracted substantial attention as new components of disease mechanisms and as potential biomarkers in multiple diseases, including cancer. CircRNAs are often highly conserved and exhibit developmental stage- and disease-specific expression. Several studies have reported circRNA expression patterns that are associated with specific cancer types and with patient prognosis. Here, we overview the active registered clinical trials that investigate the value of circRNAs as cancer biomarkers and discuss the potential of circRNAs in clinical cancer care. Taken together, circRNAs are actively being investigated as diagnostic, predictive, and prognostic biomarkers, and their potential to serve as therapeutic intervention points motivates ongoing translational and clinical research.